The primary goals of this research are i) to establish the changes in brain processing arising from nervous system damage or dysfunction, ii) to understand how brain plasticity contributes to these changes, and iii) to determine how learning may ameliorate the negative consequences of such changes. Over the past year we have continued to focus primarily on plasticity following the loss of input to particular regions of the brain, including visual and somatosensory cortex. i) Loss of visual input. People with macular degeneration lose central vision due to retinal damage. But what happens to the parts of the brain that are specifically involved in processing central visual stimuli? Using fMRI, we have previously shown that the parts of the brain deprived of input start to respond to visual stimuli in other regions of the visual field, as if they are taking on new function. We have referred to this as reorganization of visual processing. We have further demonstrated that such reorganization is dependent on complete loss of central vision, is not specific to the part of the retina used for fixation in people with macular degeneration (often referred to as the Preferred Retinal Locus, or PRL), and may lead to perceptual distortions. We are currently investigating the impact of vision loss in macular degeneration on cortical thickness. In some developmental visual disorders, the cortex has been reported to be thinner than in healthy control participants, but it is unknown whether such structural changes also occur when the vision loss happens in adulthood. ii) Loss of somatosensory input. Following limb amputation, over 90% of people report phantom sensations in their missing limb, often painful sensations (Phantom Limb Pain, or PLP). One current theory suggests that PLP is a direct result of cortical reorganization, an example of maladaptive plasticity. Mirror therapy has been used as a treatment for PLP. During this therapy, patients move their intact limb while looking in a mirror, making it seem as if their missing limb is moving. We are currently investigating the neural consequences of amputation and the impact of mirror therapy on brain activity over time. We are continuing to recruit unilateral limb amputees and monitoring brain activity with fMRI over a period of four weeks while the amputees undergo mirror therapy. We are trying to establish whether the presence of PLP correlates with cortical reorganization in the somatosensory and motor cortex (similar to that observed in our participants with macular degeneration) and whether the mirror therapy works by reducing the extent of cortical reorganization. Establishing the nature, degree and consequences of plasticity in the adult cortex provides important insights into the potential for rehabilitative brain therapies following injury or dysfunction in the nervous system.